Thomas H. Morton

Biography

Ongoing efforts in this research group are evenly divided between gas-phase ion chemistry (with a view toward being able to predict mass spectra from first principles) and neuroscience-related projects:

Covalent modification of receptor sites involved in vertebrate olfaction. We have demonstrated, by use of a behavioral assay, that it is possible to block selectively the olfactory detection of aldehydes and ketones. This specific odor blindness ("selective hyposmia") is produced by sequential application of acetoacetic ester followed by cyanoborohydride directly to the receptor epithelia of experimental animals and is congruent to chemistry that we have examined for Schiff base-forming proteins in vivo. Using radiolabeled reagents we have isolated a membrane-bound protein that is unique to the olfactory epithelium, which we believe is one receptor type involved in the sense of smell.

An alternative approach for isolation of cell-surface receptors involves biotin-avidin labelling. We seek to attach biotin irreversibly to an olfactory receptor, so that membrane patches containing functional transducing units can be purified. Since cells contain a number of biotinylated proteins to begin with, an avidin affinity column cannot be expected to provide a sufficient degree of purification by itself. We have therefore synthesized a series of silicon-containing extender arms that can be hydrolyzed by catalytic action of fluoride ion. This provides an additional stage of purification: sequestration of biotinylated fractions by avidin as the first stage, followed by selective release of units that are connected to biotin via the fluoridolyzable linker as the second. We call this new technique "two-step affinity chromatography."